Showing papers in "The Journal of Physiology in 1969"

A Theory of Cerebellar Cortex

Abstract: 1. A detailed theory of cerebellar cortex is proposed whose consequence is that the cerebellum learns to perform motor skills. Two forms of input-output relation are described, both consistent with the cortical theory. One is suitable for learning movements (actions), and the other for learning to maintain posture and balance (maintenance reflexes). 2. It is known that the cells of the inferior olive and the cerebellar Purkinje cells have a special one-to-one relationship induced by the climbing fibre input. For learning actions, it is assumed that: (a) each olivary cell responds to a cerebral instruction for an elemental movement. Any action has a defining representation in terms of elemental movements, and this representation has a neural expression as a sequence of firing patterns in the inferior olive; and (b) in the correct state of the nervous system, a Purkinje cell can initiate the elemental movement to which its corresponding olivary cell responds. 3. Whenever an olivary cell fires, it sends an impulse (via the climbing fibre input) to its corresponding Purkinje cell. This Purkinje cell is also exposed (via the mossy fibre input) to information about the context in which its olivary cell fired; and it is shown how, during rehearsal of an action, each Purkinje cell can learn to recognize such contexts. Later, when the action has been learnt, occurrence of the context alone is enough to fire the Purkinje cell, which then causes the next elemental movement. The action thus progresses as it did during rehearsal. 4. It is shown that an interpretation of cerebellar cortex as a structure which allows each Purkinje cell to learn a number of contexts is consistent both with the distributions of the various types of cell, and with their known excitatory or inhibitory natures. It is demonstrated that the mossy fibre-granule cell arrangement provides the required pattern discrimination capability. 5. The following predictions are made. (a) The synapses from parallel fibres to Purkinje cells are facilitated by the conjunction of presynaptic and climbing fibre (or post-synaptic) activity. Reprinted with permission of The Physiological Society, Oxford, England. (b) No other cerebellar synapses are modifiable. (c) Golgi cells are driven by the greater of the inputs from their upper and lower dendritic fields. 6. For learning maintenance reflexes, 2(a) and 2 (b) are replaced by 2’. Each olivary cell is stimulated by one or more receptors, all of whose activities are usually reduced by the results of stimulating the corresponding Purkinje cell. 7. It is shown that if (2’) is satisfied, the circuit receptor → olivary cell → Purkinje cell → effector may be regarded as a stabilizing reflex circuit which is activated by learned mossy fibre inputs. This type of reflex has been called a learned conditional reflex, and it is shown how such reflexes can solve problems of maintaining posture and balance. 8. 5(a), and either (2) or (2’) are essential to the theory: 5(b) and 5(c) are not absolutely essential, and parts of the theory could survive the disproof of either.

On the existence of neurones in the human visual system selectively sensitive to the orientation and size of retinal images.

Abstract: 1. It was found that an occipital evoked potential can be elicited in the human by moving a grating pattern without changing the mean light flux entering the eye. Prolonged viewing of a high contrast grating reduces the amplitude of the potential evoked by a low contrast grating. 2. This adaptation to a grating was studied psychophysically by determining the contrast threshold before and after adaptation. There is a temporary fivefold rise in contrast threshold after exposure to a high contrast grating of the same orientation and spatial frequency. 3. By determining the rise of threshold over a range of spatial frequency for a number of adapting frequencies it was found that the threshold elevation is limited to a spectrum of frequencies with a bandwidth of just over an octave at half amplitude, centred on the adapting frequency. 4. The amplitude of the effect and its bandwidth are very similar for adapting spatial frequencies between 3 c/deg. and 14 c/deg. At higher frequencies the bandwidth is slightly narrower. For lower adapting frequencies the peak of the effect stays at 3 c/deg. 5. These and other findings suggest that the human visual system may possess neurones selectively sensitive to spatial frequency and size. The orientational selectivity and the interocular transfer of the adaptation effect implicate the visual cortex as the site of these neurones. 6. This neural system may play an essential preliminary role in the recognition of complex images and generalization for magnification.

The effects of length and stimulus rate on tension in the isometric cat soleus muscle

Abstract: 1. By subdividing ventral roots and supplying stimulating pulses to different groups of motor units in rotation, smooth contractions of soleus could be obtained with low rates of stimulation. 2. Isometric tension was recorded with different rates of stimulation, and at different muscle lengths. 3. Longitudinal histological sections were cut from muscles fixed at different lengths, and sarcomeres were measured. Mean sarcomere lengths in soleus could then be related to the angle at the ankle. 4. At high rates of stimulation the maximum active tension was obtained at a length corresponding to an angle of about 60° at the ankle, and a mean sarcomere length of about 2·8 μ. The isometric tension fell only slightly on shortening the muscle to a length equivalent to 100°, and a mean sarcomere length about 2·3 μ. Further shortening caused a marked fall in tension. 5. There was a reciprocal relationship between stimulus rate and muscle length; when the muscle was long low rates of stimulation gave near maximal tension, whereas at short lengths the maximum tension was reached only when the stimulus rate was very high. It is suggested that stimulating pulses activate the contractile machinery of the muscle more effectively at long than at short muscle lengths. 6. When at low rates of stimulation pulses were distributed among the motor units in rotation to give a smooth contraction, the tension rose higher than during the unfused tetanus that accompanied synchronous stimulation of the same motor units at the same rate. It is suggested that in an unfused tetanus internal movement of the muscle reduces the tension below that developed in a truly isometric state. 7. The rate of rise of tension in an isometric tetanus varied with both muscle length and rate of stimulation. At each stimulus rate there was a range of lengths in which the isometric tension developed slowly, this was the same length range in which, at that stimulus rate, the length tension curve was steep.

The influence of calcium on sodium efflux in squid axons.

Abstract: 1. Previous work has shown that the sodium efflux from the axons of Loligo forbesi increases when external sodium is replaced by lithium. 2. The increase in efflux in lithium was unaffected by ouabain but was abolished by removal of external calcium; in these respects it differed from the potassium-dependent sodium efflux which was abolished by ouabain but not reduced by removal of external calcium. 3. Strontium but not magnesium could replace calcium in activating the ouabain-insensitive sodium efflux; lanthanum had an inhibitory effect. 4. Replacing all the external NaCl by choline chloride or dextrose gave a rise in Na efflux which was abolished by ouabain but not by removal of external calcium. 5. The rise in Na efflux resulting from partial replacement of NaCl by dextrose or choline chloride consisted of two components one of which was ouabain-insensitive and calcium-dependent and the other was inhibited by ouabain but calcium-insensitive. 6. The ouabain-insensitive component of the Na efflux was activated by low concentrations of Na, Li or K but inhibited by high concentrations of Na and to a lesser extent Li. The inhibiting effect of high Na was of the kind expected if these ions displace calcium from an external site. 7. The ouabain-insensitive component of the Na efflux was abolished by cyanide, had a Q10 of 2·7; and was roughly proportional to [Na]i2. It was much more variable in magnitude than the ouabain-sensitive, potassium-dependent component of the sodium efflux. 8. The calcium influx increased five to fortyfold when external NaCl was replaced by LiCl or dextrose, the increase for Li being larger than the increase for dextrose. 9. The calcium influx from Na, Li or dextrose sea water was increased three to tenfold by increasing the internal Na about fourfold. 10. The experiments provide evidence for a coupling between an inward movement of calcium and an outward movement of sodium.

The structure and function of a slowly adapting touch corpuscle in hairy skin

Abstract: 1 Slowly adapting cutaneous mechanoreceptors, in the cat and primates, have been studied by histological and neurophysiological methods 2 Each touch corpuscle is a dome-shaped elevation of the epidermis, whose deepest layer contains up to fifty specialized tactile cells 3 Nerve plates, enclosed by the tactile cell (Merkel cells), are connected to a single myelinated axon in the dense collagenous core of the corpuscle 4 The corpuscle generated > 1000 impulses/sec when excited by vertical surface pressure The response was highly localized and showed a low mechanical threshold, the frequency being dependent upon the velocity and amplitude of the displacement There was a period of rapid adaptation before a sustained response which might continue for > 30 min 5 A quantitative analysis of the responses to excitation by displacements of differing amplitude, velocity and duration is included 6 The discharge of touch corpuscle units evoked by a mechanical stimulus was temperature-sensitive, and was enhanced by a fall in skin temperature

The influence of activity on some contractile characteristics of mammalian fast and slow muscles

Abstract: 1. The time course of contraction and relaxation in the isometric twitch of a rabbit soleus muscle becomes more rapid following tenotomy and spinal cord section. This increase in speed could be prevented by long-term electrical stimulation at frequencies of 5 or 10/sec. It was not prevented by stimulation at frequencies of 20 or 40/sec. 2. Long-term electrical stimulation of fast rabbit and cat muscles at a frequency of 10/sec had a slowing effect on the time course of contraction and relaxation. 3. It is concluded that the almost continuous low frequency discharge of motoneurones innervating postural muscles plays an important part in establishing and maintaining the slow time course of contraction of these muscles. The characteristically different speeds of contraction of fast and slow striated muscles can in this way be related to the different patterns of impulse activity which they normally receive.

The sensitivity of muscle spindle afferents to small sinusoidal changes of length

Abstract: 1. Nerve impulses were recorded from spindle afferents of the soleus muscle during sinusoidal changes in muscle length at frequencies from 0.03 to 300 c/s. This was done in the decerebrate cat with intact motor outflow and ;spontaneous' fusimotor activity. Computer averaging over a number of cycles was used to measure the response, in impulses/sec, at different phases of the cycle.2. A linear range was described in which the discharges of the endings were approximately sinusoidally modulated, and in which increasing the amplitude of the stretching produced a proportional increase in the response. At 1 c/s the linear range extended up to only about 0.1 mm for primary endings, but was greater than 1 mm for secondary endings.3. The sensitivity of an ending in its linear range was defined as the amplitude of its response divided by the amplitude of the length change. The sensitivity of both primary and secondary endings increased progressively on increasing the frequency of stretching above 1 c/s. The experimental observations relating the sensitivity to the sinusoidal frequency were fitted over much of the range by a curve given by the vector sum of components proportional to the length and to the velocity of stretching. This curve has two parameters, a sensitivity at low frequencies (S), and a corner frequency (F) at which the length and velocity contributions are equal. The value of F was about 1.5 c/s for both primary and secondary muscle spindle endings. The value of S was very much greater for primary endings (median value 95 impulses/sec/mm) than for secondary endings (median value 7 impulses/sec/mm). The increasing sensitivity of the endings at higher frequencies caused a progressive reduction in the linear range when it was expressed as an amplitude of stretching, but it remained approximately constant when it was expressed as a modulation of the frequency of discharge.4. The primary endings were also extremely sensitive to maintained changes in length provided they were of sufficiently small amplitude.5. In the presence of fusimotor activity a high sensitivity of small changes was found over a wide range of muscle lengths. De-efferented endings had a comparable high sensitivity when the muscle was at or beyond physiological full extension, but not when the muscle was shorter.6. The results are contrasted with those obtained previously using stretches of large amplitude, and the physiological significance of the high sensitivity of primary endings to small stretches is discussed in relation to the reflex control of movement.

Tetrodotoxin-resistant electric activity in presynaptic terminals

Abstract: 1. The electric properties of the giant synapse in the stellate ganglion of the squid have been further investigated.2. During tetrodotoxin (TTX) paralysis, a local response can be elicited from the terminal parts of the presynaptic axons after intracellular injection of tetraethyl ammonium ions (TEA).3. The response is characterized by an action potential of variable size and duration, whose fall is often preceded by a prolonged plateau. The response, especially the duration of the plateau, is subject to ;fatigue' during repetitive stimulation.4. The TTX-resistant form of activity is localized in the region of the synaptic contacts, and shows a marked electrotonic decrement even within less than 1 mm from the synapse. It is found only on the afferent, not on the efferent, side of the synapse.5. During the plateau of the response, the membrane resistance is greatly reduced below its resting value.6. The response depends on presence of external calcium and increases in size and duration with the calcium concentration. Strontium and barium substitute effectively for calcium. Manganese and, to a lesser extent, magnesium, counteract calcium and reduce the response. The response also declines, and ultimately disappears, if sodium is withdrawn for long periods.7. The relation of the local TTX-resistant response to the influx of calcium ions and to the release of the synaptic transmitter is discussed.

Calcium movements across the membrane of human red cells.

Abstract: 1. A study has been made of the cellular content and movement of Ca across the membrane of human red blood cells. 2. The [Ca] in the cellular contents of fresh red cells is 4·09 × 10-2 mM. The intracellular concentration of free ionic Ca ([Ca2+]) is considered to be less than this value and therefore less than extracellular [Ca2+] under normal conditions. 3. Observation of unidirectional Ca fluxes with 45Ca confirms previous reports of low permeability of the red cell membrane for Ca. After nearly 1 week of loading in the cold, intracellular 45Ca content is 1·8% of extracellular 45Ca content. Appearance in extracellular fluid of 45Ca from coldloaded cells can be considered to arise from two compartments. Efflux of 45Ca from the `slower compartment' is accelerated by the addition of glucose. 4. Starved red cells, incubated at 37° C, after reversible haemolysis for loading with Ca and Mg-ATP, exhibit an outward net transport of Ca against an electrochemical gradient. The transport is associated with the appearance of inorganic phosphate (Pi). Cells treated similarly, but without ATP show no transport and no appearance of Pi. 5. During the initial phase of transport, 1·3 mole Pi appear per mole Ca transported. 6. The transport of Ca from ATP-loaded cells is highly temperature-dependent, with a Q10 of 3·5. 7. Cell membrane adenosine triphosphatase (ATPase) activity of reversibly haemolysed cells is stimulated only by intracellular, and not by extracellular Ca. 8. Neither Ca transport in reversibly haemolysed cells, nor the Ca-Mg activated ATPase of isolated cell membranes is sensitive to Na, K, ouabain or oligomycin. 9. Mg is not transported under the conditions which reveal Ca transport, but Mg appears to be necessary for Ca transport. 10. Sr is transported from reversibly haemolysed Mg-ATP-loaded cells. Sr also can substitute for Ca, but not for Mg, in the activation of membrane ATPase. 11. It is concluded that, in addition to a low passive permeability, an active extrusion mechanism for Ca exists in the human red cell membrane. This extrusion mechanism, in addition to a low passive membrane permeability for Ca, may represent the means by which intracellular Ca content is maintained at a low level. It is suggested that the Ca-Mg activated membrane ATPase and the active transport of Ca are two manifestations of the same process.

The mechanical properties of cat soleus muscle during controlled lengthening and shortening movements

Abstract: 1. By supplying pulses to different subdivisions of the ventral nerve roots in rotation, it was possible to obtain smooth contractions of cat soleus with low rates of stimulation. 2. After contracting isometrically the muscle was subjected to constant velocity lengthening or shortening movements. 3. During shortening the tension always fell below the isometric value. The fall in tension was usually greatest when low rates of stimulation were used. 4. The effect of lengthening on tension depended on the rate of stimulation. At high rates of stimulation the tension during lengthening always rose above the isometric tension. At lower rates of stimulation (5-15 pulses/sec) the tension rose at the beginning of an extension, but decreased later in the movement to a level that was often less than the isometric tension corresponding to that muscle length. At these stimulus rates the tension during isometric contraction was usually higher than during a sustained movement in either direction. 5. At low rates of stimulation longitudinal vibratory movements of more than 0·1 mm also reduced the tension far below the isometric value, whereas the reduction was quite slight when the rate of stimulation was high. 6. The isometric tension during smooth contractions at low stimulus rates was remarkable in the following respects: it developed rather slowly, it was higher than the tension during or immediately after movements, and it was only slowly regained after movement had ceased. 7. The results are discussed in relation to the sliding filament theory of muscle contraction, which, with certain assumptions, provides an explanation for many of the findings.

Outward membrane currents activated in the plateau range of potentials in cardiac Purkinje fibres

Abstract: 1. The membrane currents in Purkinje fibres under voltage clamp conditions have been investigated in the range of potentials at which the action potential plateau occurs. The results show that in this range slow outward current changes occur which are quite distinct from the potassium current activated in the pace-maker range of potentials. 2. The time course of current change in response to step voltage changes is non-exponential. At each potential the current changes may be analysed in terms of the sum of two exponential changes and this property has been used to dissect the currents into two components, ix1 and ix2, both of which have been found to obey kinetics of the Hodgkin—Huxley type. 3. The first component, ix1, is activated with a time constant of about 0·5 sec at the plateau. At more positive and more negative potentials the time constants are shorter. The steady-state degree of activation varies from 0 at about -50 mV to about 1 at +20 mV. The instantaneous current—voltage relation is an inward-going rectifier but shows no detectable negative slope. In normal Tyrode solution ([K]0 = 4 mM) the reversal potential is about -85 mV. 4. The second component, ix2, is activated extremely slowly and the time constant at the plateau is about 4 sec. The steady-state activation curve varies from 0 at about -40 mV to 1 at about +20 mV. The instantaneous current—voltage relation is nearly linear. The reversal potential occurs between -50 and -20 mV in different preparations. 5. It is suggested that these currents are carried largely by K ions, but that some other ions (e.g. Na) also contribute so that the reversal potentials are positive to EK. 6. The relation of these results to previous work on delayed rectification in cardiac muscle is discussed.

Mechanism of stimulation of type J pulmonary receptors

Abstract: 1. The responses of type J pulmonary receptors (identified according to existing criteria) were studied in anaesthetized cats by recording impulses in individual vagal afferent fibres whose conduction velocity ranged from 0.8 to 7 m/sec.2. Measurements of actual latencies between insufflation of halothane or ether into the lungs and the excitation of the endings, and the latencies before and after circulatory arrest have established that the endings are located in the interstitial tissues close to the pulmonary capillaries. Mainly for this reason, the term juxta-pulmonary capillary receptors (i.e. type J receptors) has been applied to these endings in preference to the term K deflation receptors used hitherto.3. The endings were stimulated by pulmonary congestion produced by occlusion of the aorta or left a-v junction for short periods. They were markedly stimulated during pulmonary congestion following injection of alloxan (150 mg/kg) or the addition of chlorine to the inspired air. This excitation was associated with a marked rise in pulmonary artery pressure and the occurrence of pulmonary oedema. However, the actual onset of excitation occurred some time after the rise in pressure and it was in fact more closely related to fall in pulmonary compliance. The frequency of discharge averaged over about 10-20 sec (in order to take the periods of relative inactivity into account) was 7.5 impulses/sec in 10 fibres (range 0.6-19 impulses/sec; S.D. 6.3). This is intense stimulation of the endings and the congestion so produced is therefore regarded as a severe stimulus for the endings.4. The pattern of excitation was variable. In some fibres the activity consisted of periodic bursts of impulses which seemed to be set off during the deflation phase of artificial respiration, sometimes during the inflation phase. This periodic activity was not due to contraction of smooth muscle as the endings are not stimulated following injection of histamine (into the right ventricle) which is known to stimulate smooth muscles in the alveolar ducts and respiratory bronchioles.5. It is postulated that the actual stimulus for the endings is a rise in interstitial pressure or volume produced by a rise in pulmonary capillary pressure. Evidence has been gathered to show that the latter rises during muscular exercise; this rise must stimulate the endings. It was therefore postulated that stimulation of the endings should cause reflex inhibition of limb muscles (for terminating exercise).

The effect of cyanide on the efflux of calcium from squid axons

Abstract: 1. The average rate constant for loss of 45Ca from an unpoisoned squid axon was 1·8 × 10−3 min−1, corresponding to an efflux of 0·2 p-mole/cm2 sec. 2. The Ca efflux from unpoisoned axons was reduced if external calcium was replaced with magnesium, or external sodium with lithium, choline or dextrose. Replacing both sodium and calcium reduced the efflux to about 40%. 3. Cyanide caused little immediate change in Ca efflux but after 1½-2½ hr the efflux increased to 5-15 times its normal value. The effect was rapidly reversed when cyanide was removed. 4. The large Ca efflux into cyanide was reduced by a factor of three when external calcium was replaced with magnesium and by a further factor of about six when external sodium was replaced with lithium. 5. The Ca efflux from both poisoned and unpoisoned axons had a Q10 of 2-3, was not affected by ouabain and was greatly reduced by injecting ethyleneglycol bis (aminoethylether)-N,N′-tetra-acetic acid (EGTA). 6. After injecting 45Ca along the axis, the efflux of calcium reached its maximum much more rapidly in a cyanide-treated axon than in an unpoisoned axon. 7. Pre-treatment with cyanide greatly increased the rate at which calcium was lost from axoplasm extruded into flattened dialysis bags. A similar effect was observed when cyanide was applied after extrusion. 8. Replacing external sodium glutamate with potassium glutamate greatly reduced the loss of 45Ca from intact axons poisoned with cyanide but had little effect on the loss from extruded axoplasm. 9. The rate constant for loss of the Ca EGTA complex was about 3 × 10−5 min−1 for intact axons and 2 × 10−2 min−1 for extruded axoplasm. 10. A possible explanation of the cyanide effect is that, after poisoning, calcium ions are released from a store and can then exchange at a higher rate with external sodium or calcium. 11. The experiments suggest that part of the calcium efflux may be coupled to sodium entry. 12. Theoretical equations for ‘diffusion and chemical reaction in a cylinder’ are described in the Appendix.

Effect of barbiturates on `quantal' synaptic transmission in spinal motoneurones

Abstract: 1. Monosynaptic excitatory post-synaptic potentials (EPSPs) produced in triceps surae motoneurones of the cat by stimulation of single afferent fibres in the muscle nerve were recorded with intracellular electrodes before and after the administration of thiopentone or pentobarbitone. 2. The average amplitude of the ‘unit’ EPSP was 0·11–0·21 mV and remained unchanged after the administration of the barbiturates (10 mg/kg, I.V.). 3. Mean quantum content (m) ranged from 1·9 to more than 5 before drug administration. The m was reduced by thiopentone (10 mg/kg, I.V.) and pentobarbitone (10 mg/kg, I.V.) by 23·1 and 24·7% respectively. 4. The barbiturates, in the doses employed, produced no alterations in the input resistance of the motoneurone membrane or in the strength—duration relation obtained by passing depolarizing current pulses through the micro-electrode. 5. It is concluded that the action of thiopentone and pentobarbitone, in the doses used, is confined to the presynaptic nerve terminals and results in a reduction in the amount of transmitter released by afferent impulses.

The spatial selectivity of the visual cells of the cat.

Abstract: 1. Micro-electrode recordings have been made from single units in the visual cortex of the cat, during stimulation by moving grating patterns generated on a cathode ray tube. 2. The responses of the units have been measured in terms of either the frequency of impulses, or the contrast sensitivity, and expressed as a function of the spatial frequency of the grating pattern. 3. The amplitude of the responses recorded from cortical cell bodies was dependent upon the orientation of the moving grating, and for these units the stimulus was always presented at the preferred orientation. The response amplitude of other units did not depend upon the orientation of the grating stimulus, and these are believed to be the terminations of geniculate fibres. 4. The high spatial frequency end of the response function measured in terms of the contrast sensitivity could be well fitted by an exponential function. Subtraction of the blank count from the impulse frequency data gave a curve fitted by the same exponential function. The low frequency end was less consistent. 5. The spatial frequency at which this exponential function had fallen by one log. unit was taken to specify the position of the unit's response in the spatial frequency spectrum. For all units these values cover a range of four octaves of spatial frequency (from 0·18 to 3·8 cycles per degree). 6. It is suggested that these neurophysiological results support psychophysical evidence for the existence in the visual system of channels, each selectively sensitive to a narrow band of spatial frequencies.

A study of the action of picrotoxin on the inhibitory neuromuscular junction of the crayfish

Abstract: 1. The effect of picrotoxin on the neuromuscular junction of the crayfish (Cambarus clarkii) was investigated. The potential changes were recorded intracellularly and extracellularly with micro-electrodes. The membrane conductance of the muscle fibre was also measured. 2. Picrotoxin depressed the amplitudes of the inhibitory junctional potentials and the potential changes produced by iontophoretically applied γ-aminobutyric acid (GABA), but had no appreciable effect on the excitatory junctional potentials and the potential changes produced by L-glutamate. 3. The presynaptic action of GABA and the neural transmitter was depressed by picrotoxin. The presynaptic action of β-guanidinopropionic acid was also depressed by picrotoxin. 4. The increase in the membrane conductance produced by the addition of GABA in the bath fluid was depressed by picrotoxin. The dose—response relation showed that picrotoxin depressed the conductance increase produced by GABA in a non-competitive manner. The action of picrotoxin on the conductance increase produced by GABA was more effective in low Cl- solution. 5. The analysis of the dose—response curves showed that the action of picrotoxin was well expressed by the Michaelis—Menten equation, but the slope of the dose—response curve of GABA was steeper than this relation. It is proposed that the conductance of the junctional membrane was increased by the combination of two molecules of GABA with a receptor, and the attachment of one molecule of picrotoxin to a specific site depressed the conductance increase.

Characteristics of knee joint receptors in the cat.

Abstract: 1. The conduction velocities of 278 posterior articular nerve fibres studied in dorsal root filaments ranged from 10 to 110 m/sec. The conduction velocities were distributed similarly to posterior articular nerve fibre diameters determined histologically. 2. Two hundred and nine fibres were slowly adapting. Of these, 140 responded only at both marked flexion and marked extension, forty-seven responded only during flexion and twelve only during extension. Four slowly adapting fibres were activated specifically at intermediate joint positions. Outward twist of the tibia (abducting the foot) enhanced the discharge of most slowly adapting joint fibres. 3. Two rapidly adapting receptor types were noted. Pacinian corpuscle-like receptors (fourteen fibres) responded transiently to joint movement in any direction regardless of initial position. Phasic joint receptors (thirty fibres) were rapidly adapting at most joint positions but could give a low rate sustained discharge when strongly stimulated. 4. Six slowly adapting posterior articular nerve fibres responded to succinylcholine, suggesting that they originated from muscle spindles. Spindle-like receptors were usually tonically active at intermediate joint positions. 5. Eleven slowly conducting myelinated fibres responded only to extreme joint movement, which was probably noxious.

Muscular, bronchomotor and cardiovascular reflexes elicited by mechanical stimulation of the respiratory tract

Abstract: 1. The effects of mechanical stimulation in the nose, epipharynx, laryngopharynx and tracheobronchial tree, and of chemical irritation of the nasal mucosa, were studied on various somatic and autonomic functions in cats.2. Action potentials were recorded from the diaphragm and rectus abdominis muscles of spontaneously breathing cats, and from the phrenic and lumbar nerves of paralysed, artificially ventilated cats. Expulsive processes such as sneezing and coughing evoked from the nasal, laryngopharyngeal and tracheobronchial mucosae were characterized by strong diaphragmatic and abdominal expiratory discharges; synchronous discharges in these antagonistic respiratory muscles and their motoneurones often occurred especially during laryngopharyngeal stimulation of coughing.3. The ;aspiration reflex' elicited from the epipharynx was characterized by brief bursts of high-frequency activity in the phrenic nerve and diaphragm, and was usually not followed by any expiratory activity in the rectus abdominis or its motoneurones.4. In paralysed, artificially ventilated cats stimulation of the laryngeal and tracheobronchial regions caused large increases both in total lung resistance and in tracheal constrictor nerve fibre activity, indicating reflex tracheo-bronchoconstriction; similar stimulation of the epipharyngeal and nasal mucosae decreased both total lung resistance and tracheal constrictor nerve fibre activity, indicating reflex bronchodilation.5. In paralysed cats, stimulation of each of the four sites in the respiratory tract caused a reflex increase in systemic blood pressure, the largest hypertensive response coming from the epipharynx. Nervous activity in cervical sympathetic efferent fibres was increased by the stimulations, especially those of the epipharyngeal and laryngopharyngeal regions.6. There was good correlation in time and magnitude between the changes in total lung resistance and in bronchoconstrictor fibre activity, and also between the changes in blood pressure and in efferent sympathetic discharge, although the mechanical changes lagged behind the nervous ones.7. In anaesthetized, spontaneously breathing cats stimulation of the respiratory tract evoked large variations in blood pressure accompanying the spasmodic respiratory efforts, probably by mechanical effects.

Cutaneous thermoreceptors in primates and sub-primates.

Abstract: 1. Cutaneous thermoreceptors were examined electrophysiologically in primates (monkey, baboon) and in sub-primates (dog and rat) by recording from single units dissected from peripheral nerves.2. Thermal stimuli were delivered from thermodes in contact with the skin.3. Primate ;cold' receptors had spot-like receptive fields and were found in both hairy and glabrous skin. The conduction velocities of the axons ranged from 0.6 to 15.3 m/sec.4. The discharge from the primate receptors characteristically appeared in bursts with intervals of silence within the range temperatures of 18-40 degrees C. Static and dynamic sensitivity curves were established, with maxima about 30 degrees C.5. Cold receptors in the lip of the dog had maximal sensitivity at 31-37 degrees C. The axons were myelinated with conduction velocities less than 20 m/sec.6. ;Warm' receptors, with maximal sensitivity at 40 degrees C and non-myelinated axons, were abundant in the scrotal nerve of the rat. The ;cold' receptors had maximal responses at 23-28 degrees C.7. The ;spurious' thermoreceptor behaviour of slowly adapting mechanoreceptors is described and the way in which they may distort integrated potential records from whole nerves is analysed.

Spontaneous and evoked activity of motor nerve endings in calcium Ringer

Abstract: 1. Electrical activity of neuromuscular junctions of the frog was studied in a medium (Ca-Ringer) whose Na ions had been entirely replaced by Ca. 2. Spontaneous miniature end-plate potentials (m.e.p.p.s) of reduced amplitude are recorded in this abnormal ionic environment, and graded end-plate potentials can be elicited by applying depolarizing current pulses to the pre-junctional parts of the nerve. 3. Addition of 5 m M tetraethylammonium (TEA) to the Ca-Ringer causes the appearance, in almost all-or-none fashion, of very large e.p.p.s (up to 45 mV in amplitude) in response to nerve stimulation. 4. These ‘giant’ e.p.p.s occur despite the curarizing action of TEA (and its depressing effect on the amplitude of m.e.p.p.s) and they persist after application of tetrodotoxin. 5. After several hours exposure to Ca-Ringer, spontaneous end-plate activity gradually declines, and eventually evoked e.p.p. responses fail. On return to normal Na-Ringer, spontaneous end-plate activity is quickly resumed, but the potentials have an abnormal, very wide, amplitude distribution. 6. The results are discussed, in conjunction with relevant work on the squid giant synapse, in terms of the ‘calcium hypothesis’ of transmitter release.

Force measurements in skinned muscle fibres

Abstract: 1. Isometric force was measured in skinned segments of frog semitendinosus muscle fibres exposed to solutions in which the calcium ion concentration was controlled with EGTA.2. The threshold for force development, calculated from an apparent stability constant for the CaEGTA complex of 10(6.69)M(-1) at pH 7.0, was generally close to pCa 7.5. Maximum force was reached at about pCa 6.0.3. Maximum force is proportional to the cross-sectional area of the fibres.4. The rate of force development was slower than that expected from simple diffusion of a substance from the bathing solution into the fibre. The delay appears to be due to slow equilibration of the EGTA buffer system during calcium uptake by the sarcoplasmic reticulum.5. Addition of deoxycholate (DOC) to the bathing solution produced a reversible increase in the rate of force development. The steady force was also increased for values of pCa that gave less than maximum force, which shifted the force-pCa relation toward lower calcium concentrations by about 0.5 pCa unit.6. The length-force relation in partially activated preparations is similar to that reported for electrically activated intact fibres. This result suggests that in the region of myofilament overlap the affinity of the binding sites for calcium is uniform along the length of the calciumbinding myofilament.

Changes in the maintained discharge with adaptation level in the cat retina

Abstract: 1. The mean rate, impulse interval distribution, and pulse number distribution of the maintained discharge of ganglion cells in the retina of the cat have been studied after prolonged adaptation at different luminance levels.2. From a state of complete dark adaptation up to a luminance of about 5 x 10(-3) cd/m(2) (viewed through a 7 mm(2) pupil) the mean rate of on-centre units increases. From darkness up to a somewhat higher luminance the mean rate of some off-centre units decreases, but others show little change.3. Above 10(-2) cd/m(2) the mean rate ceases to show a regular relation with adaptation level. On units often decrease and then increase again at a higher level. Rhythmical fluctuations are common near 10(-2) cd/m(2), especially if the retina is not in first class condition. Mean rates above 70/sec and below 1/sec are very rare at any adaptation level.4. Over the range where mean rate increases monotonically with adaptation level, it is shown that the surround of on-centre units does not inhibit and off responses cannot be elicited. When the monotonic increase is slowed or reversed it becomes possible to elicit responses from the surround. We suspect that the surround exerts a sustained, tonic, inhibiting effect at higher adaptation levels, thus holding down the maintained discharge.5. There are rare units, forming less than 1% of those isolated, that show a regularly increasing frequency with increase of adaptation level above 10(-2) cd/m(2). These units have concentric ;on' and ;off' zones in their receptive fields, but the responses to rapidly changing stimuli are sluggish and they have an unusually regular maintained discharge. They have been tentatively called ;luminance units'.6. The impulse-interval and pulse-number distributions of on-centre units change predictably with adaptation level; the variance of the pulse number distribution is usually several times the mean at very low adaptation levels, but only a fraction of the mean at high levels. Off-centre units do not show predictable changes. Luminance units fire more regularly, and have narrower pulse-number and impulse interval distributions than other concentric units.7. A simple model is proposed to account for the statistical characteristics of the maintained discharge of on-centre units.

The effect on drinking in the rat of intravenous infusion of angiotensin, given alone or in combination with other stimuli of thirst.

Abstract: 1. Intravenous infusion of angiotensin causes rats which are in water balance to drink water.2. The mean amount of angiotensin needed to initiate drinking was 29.1 +/- 4.6 mug/kg (S.E. of mean) in twenty normal rats, and 15.7 +/- 2.1 mug/kg in thirty-four nephrectomized rats.3. The nephrectomized rat is therefore more sensitive to this action of angiotensin than the rat with intact kidneys.4. The rates of infusion (0.05-3.0 mug/kg(-1) min(-1)) which cause drinking are comparable to those used to produce other effects in rats.5. Angiotensin restores the drinking response of the nephrectomized rat subjected to caval ligation to a value similar to that obtained in the uninfused normal rat subjected to caval ligation.6. The effects of angiotensin and hypertonic saline on drinking are additive when both substances are administered to nephrectomized rats.7. These experiments provide further support for the view that the renin-angiotensin system is concerned in extracellular thirst.

The ouabain-sensitive fluxes of sodium and potassium in squid giant axons.

Abstract: 1. Fifty to ninety per cent of the Na efflux from axons of Loligo forbesi is inhibited by ouabain. The properties of the ouabain-sensitive component of the Na efflux are different from those of the ouabain-insensitive component. 2. In unpoisoned axons with an average Na content of 75 m-mole/kg axoplasm the bulk of the ouabain-sensitive Na efflux is dependent on external K. 3. In the presence of 460 m M Na in the external medium, raising the external K concentration from 0 to 100 m M increases the ouabain-sensitive Na efflux along a sigmoid curve which shows signs of saturating at high K concentrations. 4. The curve relating ouabain-sensitive K influx to external K concentration is similar in shape to that for the ouabain-sensitive Na efflux. At all K concentrations examined the ouabain-sensitive K influx was less than the ouabain-sensitive Na efflux. 5. Potassium-free sea water acts rapidly in reducing the Na efflux. There is no appreciable difference between the rates of action of K-free sea water on the Na pump and Na-free sea water on the action potential. 6. Caesium and Rb can replace external K in activating the ouabain-sensitive Na efflux. Both the affinity and maximum rate of the Na efflux mechanism are lower when Cs replaces K as the activating cation. 7. Isosmotic replacement of external Na by either choline or dextrose, but not Li, increases the affinity of the ouabain-sensitive Na efflux mechanism for external K without appreciably affecting the maximum rate of pumping. External Li behaves like external Na and exerts an inhibitory action on the Na efflux. 8. There is a large ouabain-sensitive Na efflux into K-free choline or dextrose sea waters. Addition of either Na or Li to the external medium reduces this efflux along a section of a rectangular hyperbola. The properties of this efflux suggest that there is a residual K concentration of up to 2 m M immediately external to the pumping sites in the axolemma. 9. Over the range of internal Na concentrations studied (16-140 m-mole/kg axoplasm) the ouabain-sensitive Na efflux increased linearly with Na concentration. 10. Tetrodotoxin (10−6 g/ml.) reduces the Na influx by about half, but does not affect the ouabain-sensitive Na efflux. 11. Isobutanol (1% v/v) reversibly decreases both the ouabain-sensitive and ouabain-insensitive components of the Na efflux. 12. Application of 2 m M cyanide to axons immersed in K-free sea water produces a transient rise in the Na efflux. This rise is not seen if ouabain is included in the sea water. The rise in efflux occurs at a time when the axons are partially poisoned and contain adenosine triphosphate (ATP) but no arginine phosphate (ArgP). A similar, but maintained rise can be obtained after application of dinitrophenol (DNP) at pH 8·0. The increased Na efflux in these partially poisoned axons is also inhibited by ouabain. 13. Under conditions of partial-poisoning by alkaline DNP, there is a ouabain-sensitive Na influx from K-free sea water. The ouabain-sensitive Na influx is of similar size to the ouabain-sensitive Na efflux. These results show that in partially-poisoned axons immersed in K-free sea water intracellular Na exchanges with extracellular Na in a one-for-one manner by a ouabain-sensitive route. External Li cannot replace external Na in maintaining this process. 14. Axons partially poisoned with alkaline DNP are not insensitive to external K. In the absence of external Na their response to external K is essentially the same as that seen in unpoisoned axons. 15. Possible mechanisms are discussed for the appearance of Na-Na exchange in partially poisoned axons.

Elastic constants of the human lens capsule

Abstract: 1. A technique is described whereby the elasticity of the human lens capsule has been determined at birth and throughout life. This technique requires three separate determinations: (a) thickness; (b) stress and strain; (c) Poisson's ratio; (a) the capsule was clamped between accurately perforated ground glass plates and its thickness determined by noting the change in depth of focus between Latex spherules adhering to its upper and lower surfaces; (b) the undisturbed capsule was then placed in a specially designed glass distension apparatus and the relationship between volume and pressure recorded when it was distended with isotonic saline. The permeability of the capsule was also measured; (c) in some cases Poisson's ratio was determined by measuring the change of thickness of the capsule and the height to which it rose when distended with isotonic saline at different pressures. An apparatus was designed for this purpose.2. The average thickness of the anterior capsule increases from birth until about the 60th year but thereafter it decreases slightly.3. Poisson's ratio was about 0.47 for both cat and human capsule, and no significant variations with age in human capsule could be detected.4. Corrected volume pressure curves obeyed Hook's law almost to the point of capsule rupture.5. In childhood Young's Modulus of elasticity is about 6 x 10(7) dyn/cm(2) and decreases to 3 x 10(7) dyn/cm(2) at 60 and 1.5 x 10(7) dyn/cm(2) in extreme old age.6. The ultimate tensile stress was 2.3 x 10(7) dyn/cm(2) in young capsules and 0.7 x 10(7) dyn/cm(2) in old ones. The maximum percentage elongation was 29 per cent and independent of age.7. The implications of these findings are discussed in relation to(a) the mechanical properties of the lens capsule;(b) the ageing of the lens capsule and basement membranes; and(c) the decrease in elasticity of the lens capsule as a cause of presbyopia.

Visual area of the lateral suprasylvian gyrus (Clare-Bishop area) of the cat.

Abstract: On anatomical and physiological grounds a zone of cat cortex deep in the medial bank of the suprasylvian sulcus (the Clare—Bishop area) is known to receive strong visual projections both from the lateral geniculate body and area 17. We have mapped receptive fields of single cells in this area in eight cats. Active responses to visual stimuli were found over most of the medial bank of the suprasylvian sulcus extending to the depths and over to the lowest part of the lateral bank. The area is clearly topographically arranged. The first responsive cells, recorded over the lateral convexity and 2-3 mm down the medial bank, had receptive fields in the far periphery of the contralateral visual fields. The receptive fields tended to be large, but showed considerable variation in size and scatter in their positions. As the electrode advanced down the bank, fields of successively recorded cells gradually tended to move inwards, so that in the depths of the sulcus the inner borders of many of the fields reached the vertical mid line. Here the fields were smaller, though they still varied very much in size. Receptive fields were larger than in 17, 18, or 19, but otherwise were not obviously different from the complex and lower-order hypercomplex fields in those areas. No simple fields, or concentric fields of the retino-geniculate type, were seen. Cells with common receptive-field orientation were grouped together, but whether or not the grouping occurs in columns was not established. Most cells were driven independently by the two eyes. Fields in the two eyes seemed to be identical in organization. Cells dominated by the contralateral eye were much more common than ipsilaterally dominated ones, but when cells with parafoveal and peripheral fields were considered separately, the asymmetry was seen to apply mainly to cells with peripheral fields.

Activity of lung irritant receptors in pulmonary micro-embolism, anaphylaxis and drug-induced bronchoconstrictions

Abstract: 1. Lung irritant receptors have been studied in rabbits by recording action potentials from single vagal nerve fibres. Some of the rabbits were bilaterally vagotomized, and some paralysed and artificially ventilated.2. The receptors gave rapidly adapting irregular discharges on inflation and deflation of the lungs. Many were stimulated by insufflation of ammonia vapour into the lungs, and some by passage of a fine catheter into the right bronchial tree. The fibres had conduction velocities in the range 3.6-25.8 m/sec.3. The receptors were strongly stimulated by intravenous injections of histamine acid phosphate, 25-100 mug/kg. The response was considerably reduced by previous injection of isoprenaline which also reduced the bronchoconstriction due to histamine.4. The receptors were stimulated by intravenous injections of isoprenaline, phenyl diguanide and micro-emboli, and by anaphylaxis induced in rabbits previously sensitized to egg albumin.5. The receptor responses could not be closely correlated in size with simultaneous changes in total lung resistance, lung compliance, tidal volume or breathing frequency.6. It is concluded that, in rabbits with intact vagus nerves, lung irritant receptors contribute to the reflex hyperpnoea and bronchoconstriction of the conditions studied.

Reflexes to sacral parasympathetic neurones concerned with micturition in the cat

Abstract: 1 Reflexes to sacral parasympathetic neurones were studied by electrophysiological techniques in decerebrate, in chloralose-anaesthetized, and in chronic spinal cats2 Excitatory reflexes from pelvic nerve and sacral somatic afferent nerve fibres were present before and after chronic transection of the spinal cord, but the latencies differed markedly It was concluded that the long-latency reflexes observed when the spinal cord was intact involved long-loop reflexes to the brain-stem The weak, short-latency reflexes in the chronic spinal cat were never observed when the spinal cord was intact and could be due to reorganized spinal connexions The short-latency reflexes are probably unimportant in normal micturition3 Stimulation of afferent fibres in the pelvic or sacral somatic nerves produced short-latency inhibitory post-synaptic potentials (IPSPs) and inhibition of discharges in parasympathetic neurones This inhibition was due to a spinal reflex4 A local reflex was demonstrated in the pelvic plexus This was probably a cholinergic axon reflex, but the remote possibility that it was a local cholinergic reflex involving sensory neurones in the bladder wall has not been excluded

Three factors limiting the reliable detection of light by retinal ganglion cells of the cat

Abstract: 1. Responses of cat retinal ganglion cells have been examined with a view to specifying the characteristics that limit the detection of light stimuli. 2. Threshold is defined as the weakest stimulus that can be reliably detected by examination of the output from a retinal ganglion cell; it depends upon (a) the quantum/spike ratio, which is the mean number of additional quantal absorptions required to produce an additional impulse, (b) the temporal course of the response, which determines the time interval within which the maintained discharge is modified, and (c) the statistical distribution of the number of impulses that occur in this time interval in the absence of the stimulus. 3. The quantum/spike ratio changes greatly when adapting luminance is changed, and this is the predominant factor accounting for changes in increment threshold. 4. The time course of the response changes with adaptation level and area of the stimulus. This may account for the changes in temporal integration that occur in analogous psychophysical experiments. 5. Changes in the irregularity of the maintained discharge also affect the threshold of single ganglion cells. This is only a minor factor in the conditions of most of our experiments, but it may be important when unstabilized images and non-equilibrium adaptation conditions are encountered.